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1.  Neurocognitive Impairment in HIV-1 Clade C versus B Infected Individuals in Southern Brazil 
Journal of neurovirology  2013;19(6):550-556.
HIV-1 clade C isolates show reduced Tat protein chemoattractant activity compared with clade B. This might influence neuropathogenesis by altering trafficking of monocytes into the CNS. A previous study suggested low rates of HIV-associated dementia in clade C infected individuals. The present study evaluated neurocognitive impairment rates in clade B- and C-infected individuals from the same local population. HIV+ and HIV- participants were recruited from the same geographic region in southern Brazil. We evaluated neuropsychological (NP) impairment using a screening instrument (the International HIV Dementia Scale; IHDS), as well as a Brazilian Portuguese adaptation of a comprehensive battery that has demonstrated sensitivity to HIV associated neurocognitive disorders (HAND) internationally. NP performance in controls was used to generate T-scores and impairment ratings by the global deficit score (GDS) method. Clade assignments were ascertained by sequencing pol and env. Blood and cerebrospinal fluid (CSF) were collected from all HIV+ participants. HIV+ and HIV- participants were comparable on demographic characteristics. HIV+ participants overall were more likely to be impaired than HIV- by the IHDS and the GDS. Clade B and C infected individuals were demographically similar and did not differ significantly in rates of impairment. The prevalence of pleocytosis, a marker of intrathecal cellular chemotaxis, also did not differ between clade B and C infections. Clade B and C HIV-infected individuals from the same geographic region, when ascertained using comparable methods, did not differ in their rates of neurocognitive impairment, and there was no evidence of differences in CNS chemotaxis.
doi:10.1007/s13365-013-0215-5
PMCID: PMC3923762  PMID: 24277437
HIV-associated neurocognitive disorders (HAND); HIV-1; clade; dementia; cerebrospinal fluid
2.  Implications of apathy and depression for everyday functioning in HIV/AIDS in Brazil 
Journal of affective disorders  2012;150(3):1069-1075.
Background
Brazil accounts for the largest number of HIV+ persons in Latin America, and this epidemic poses a significant public health burden in this country. Little is known about the neuropsychiatric and functional consequences of HIV infection in this population.
Methods
Participants were 43 HIV+ and 29 HIV- individuals who underwent a neuropsychological, psychiatric and neurological evaluation that included self-report measures of mood (Beck Depression Inventory-II; BDI-II), neurocognitive complaints (Patient's Assessment of Own Functioning Inventory) and declines in instrumental activities of daily living (Activities of Daily Living questionnaire). The MINI-Plus generated Major depressive disorder (MDD) diagnoses. Apathy, defined as social withdrawal, decision-making difficulty, loss of interest and pleasure, was measured using items from the BDI-II and the neurological evaluation.
Results
When compared with seronegative participants, HIV+ individuals endorsed higher levels of apathy spectrum symptoms. After adjusting for mood and other covariates, apathy significantly predicted worse everyday functioning.
Limitations: The small sample size, along with the self-report measures used to evaluate apathy and functional difficulties limit the inferences that may be drawn from our findings.
Conclusions
Our Brazilian HIV+ cohort endorsed apathy and depression as well as significant functional complaints. Although correlated with depression, apathy was uniquely associated with functional difficulties. Clinical attention to apathy and depression in HIV-infected Brazilians may help identify patients at risk for functional difficulties who may benefit from additional support to maintain independence.
doi:10.1016/j.jad.2012.11.040
PMCID: PMC3619015  PMID: 23245465
HIV/AIDS; Activities of Daily Living; Apathy; Depression; Brazil; Everyday functioning
3.  Increased Frequency of α-Synuclein in the Substantia Nigra in HIV Infection 
Journal of neurovirology  2009;15(2):131-138.
The frequency of neurodegenerative markers among long surviving HIV infected individuals is unknown, therefore, the present study investigated the frequency of α-synuclein, β-amyloid and HIV-associated brain pathology in the brains of older HIV infected individuals. We examined the substantia nigra of 73 clinically well-characterized HIV infected individuals aged 50 to 76 years from the National NeuroAIDS Tissue Consortium. We also examined the frontal and temporal cortical regions of a subset of 36 individuals. The brain regions were examined for the presence of α-synuclein, β-amyloid and HIV-associated brain pathology. Neuritic α-synuclein expression was found in 16% (12/73) of the substantia nigra of the HIV+ cases and none of the older control cases (0/18). β-amyloid deposits were prevalent and found in nearly all of the HIV+ cases (35/36). Despite these increases of degenerative pathology, HIV-associated brain pathology was present in only 10% of cases. Among older HIV+ adults HIV-associated brain pathology does not appear elevated; however, the frequency of both α-synuclein and β-amyloid is higher than that found in older healthy persons. The increased prevalence of α-synuclein and β-amyloid in the brains of older HIV-infected individuals may predict an increased risk of developing neurodegenerative disease.
doi:10.1080/13550280802578075
PMCID: PMC3979854  PMID: 19115126
HIV; Brain Pathology; Aging; Substantia Nigra; Cognition
4.  Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers 
AIDS (London, England)  2012;26(18):2327-2335.
Objective
The apolipoprotein E (APOE) ε4 allele enhances cerebral accumulation of β-amyloid (Aβ) and is a major risk factor for sporadic Alzheimer’s disease (AD). We hypothesized that HIV-associated neurocognitive disorders (HAND) would be associated with the APOE ε4 genotype and cerebral Aβ deposition.
Design
Clinico-pathological study of HIV-infected adults from four prospective cohorts in the U.S. National NeuroAIDS Tissue Consortium.
Methods
We used multivariable logistic regressions to model outcomes (Aβ plaques [immunohistochemistry] and HAND [standard criteria]) on predictors (APOE ε4 [allelic discrimination assay], older age [≥ 50 years], Aβ plaques, and their two-way interactions) and co-morbid factors.
Results
Isocortical Aβ deposits generally occurred as diffuse plaques and mild to moderate amyloid angiopathy. Isocortical phospho-Tau-immunoreactive neurofibrillary lesions were sparse. The APOE ε4 and older age were independently associated with the presence of Aβ plaques (adjusted odds ratio [OR] 10.16 and 5.77 [95% confidence interval (CI) 2.89–35.76 and 1.91–17.48], P=0.0003 and 0.0019, respectively, n=96). The probability of HAND was increased in the presence of Aβ plaques among APOE ε4 carriers (adjusted OR 30.00 [95% CI 1.41–638.63], P=0.029, n=15), but not in non-ε4 carriers (n=57).
Conclusion
The APOE ε4 and older age increased the likelihood of cerebral Aβ plaque deposition in HIV-infected adults. Generally Aβ plaques in HIV brains were immunohistologically different from those in symptomatic AD brains. Nonetheless, Aβ plaques were associated with HAND among APOE ε4 carriers. The detection of APOE ε4 genotype and cerebral Aβ deposition biomarkers may be useful in identifying living HAND subjects who could benefit from Aβ-targeted therapies.
doi:10.1097/QAD.0b013e32835a117c
PMCID: PMC3576852  PMID: 23018443
Apolipoprotein E; β-amyloid; HIV dementia; neurofibrillary pathology; phospho-Tau
5.  Molecular and pathologic insights from latent HIV-1 infection in the human brain 
Neurology  2013;80(15):1415-1423.
Objective:
We aimed to investigate whether HIV latency in the CNS might have adverse molecular, pathologic, and clinical consequences.
Methods:
This was a case-control comparison of HIV-1 seropositive (HIV+) patients with clinical and neuropathologic examination. Based on the levels of HIV-1 DNA, RNA, and p24 in the brain, cases were classified as controls, latent HIV CNS infection, and HIV encephalitis (HIVE). Analysis of epigenetic markers including BCL11B, neurodegeneration, and neuroinflammation was performed utilizing immunoblot, confocal microscopy, immunochemistry/image analysis, and qPCR. Detailed antemortem neurocognitive data were available for 23 out of the 32 cases.
Results:
HIV+ controls (n = 12) had no detectable HIV-1 DNA, RNA, or p24 in the CNS; latent HIV+ cases (n = 10) showed high levels of HIV-1 DNA but no HIV RNA or p24; and HIVE cases (n = 10) had high levels of HIV-1 DNA, RNA, and p24. Compared to HIV+ controls, the HIV+ latent cases displayed moderate cognitive impairment with neurodegenerative and neuroinflammatory alterations, although to a lesser extent than HIVE cases. Remarkably, HIV+ latent cases showed higher levels of BCL11B and other chromatin modifiers involved in silencing. Increased BCL11B was associated with deregulation of proinflammatory genes like interleukin-6, tumor necrosis factor–α, and CD74.
Conclusion:
Persistence of latent HIV-1 infection in the CNS was associated with increased levels of chromatin modifiers, including BCL11B. Alteration of these epigenetic factors might result in abnormal transcriptomes, leading to inflammation, neurodegeneration, and neurocognitive impairment. BCL11B and other epigenetic factors involved in silencing might represent potential targets for HIV-1 involvement of the CNS.
doi:10.1212/WNL.0b013e31828c2e9e
PMCID: PMC3662272  PMID: 23486877
6.  Impact of COMT Val158Met on executive functioning in the context of HIV and methamphetamine 
The catechol-O-methyltransferease (COMT) Val allele has been linked to executive dysfunction among healthy individuals. The nature of this relationship is unknown in the context of HIV infection and/or methamphetamine (METH) dependence, two conditions that can alter dopaminergic system functioning. We sought to determine if the putative relationship between COMT and executive dysfunction could be observed among individuals with and without HIV-infection and/or METH dependence, and to explore the specificity of this relationship by examining other cognitive domains. Utilizing an existing cohort of 229 men with and without HIV infection and/or METH dependence we found that Met/Met carriers within the HIV-only and control groups, displayed better executive functioning compared to Val/Val and Val/Met carriers. However, this effect was attenuated in the METH-only and comorbid (ie, HIV+/METH+) groups. Examination of other neurocognitive domains were not consistent with effects found for executive functioning. Results support the presumed neuroprotective effect of Met/Met genotype on executive functioning among HIV-only and control groups. Among METH-only and comorbid groups, the slower rate of dopamine clearance conferred by the Met/Met genotype may increase the risk of adverse effects of METH, resulting in comparable executive dysfunction to that of Val allele carriers.
doi:10.2147/NBHIV.S8245
PMCID: PMC3782745  PMID: 24078782
Val158Met; Endophenotype; Executive Function
7.  The Functional Impact of HIV-Associated Neuropsychological Impairment in Spanish-Speaking Adults: A Pilot Study 
Among English-speaking adults, HIV-associated neuropsychological (NP) impairments have been associated with problems in everyday functioning, including ability to function at work and drive an automobile. Latinos account for a disproportionate number of HIV/AIDS cases nationwide, and a significant segment of this population is primarily Spanish speaking. We have previously developed an assessment that evaluates English-speakers on a variety of instrumental activities of daily living. In this pilot study, we used Spanish-language translations of our functional battery to investigate the cultural relevance of such measures, and to explore relationships between NP status and ability to perform important everyday tasks in HIV-infected Spanish-speakers. Sixteen HIV-infected monolingual Spanish-speaking adults received comprehensive, Spanish language NP testing and functional assessments included the following domains: Medication Management, Cooking, Finances, Shopping, and Restaurant Scenario. Results revealed that most of the functional tasks appeared culturally relevant and appropriate with minor modifications. NP-impaired participants were significantly more functionally impaired compared to NP-normals (88% vs. 13%, p<.01). Performances on the functional assessment and the NP battery were also related to indicators of real world functioning, including employment status and quality of life. These results, though preliminary, suggest that Spanish language functional assessments are potentially valid tools for detecting everyday functioning deficits associated with NP impairments in HIV-infected Spanish-speakers.
doi:10.1076/jcen.25.1.122.13634
PMCID: PMC3737066  PMID: 12607177
8.  Preliminary evidence of motor impairment among polysubstance 3,4-methylenedioxymethamphetamine users with intact neuropsychological functioning 
Neuropsychological disturbances have been reported in association with use of the recreational drug “ecstasy,” or 3,4-methylenedioxymethamphetamine (MDMA), but findings have been inconsistent. We performed comprehensive neuropsychological testing examining seven ability domains in 21 MDMA users (MDMA+) and 21 matched control participants (MDMA−). Among MDMA+ participants, median [interquartile range] lifetime MDMA use was 186 [111, 516] doses, with 120 [35–365] days of abstinence. There were no significant group differences in neuropsychological performance, with the exception of the motor speed/dexterity domain in which 43% of MDMA+ were impaired compared with 5% of MDMA− participants (p = .004). Motor impairment differences were not explained by use of other substances and were unrelated to length of abstinence or lifetime number of MDMA doses. Findings provide limited evidence for neuropsychological differences between MDMA+ and MDMA− participants with the exception of motor impairments observed in the MDMA+ group. However, replication of this finding in a larger sample is warranted.
doi:10.1017/S1355617710000846
PMCID: PMC3737074  PMID: 20735886
Ecstasy; N-Methyl-3; 4-methylenedioxyamphetamine; Neurocognitive; Neurotoxicity; Stimulant; Hallucinogen
9.  Clinical Features and Virological Correlates of Neurocognitive Impairment among HIV-Infected Individuals in Nigeria 
Journal of neurovirology  2012;18(3):191-199.
In Nigeria the incidence and prevalence of HIV related neurocognitive impairment (NCI) are unknown and there currently exists little information related to the viral correlates rates of NCI. Therefore studies were performed to examine the potential utility of applying an established neuropsychological (NP) screening battery and detailed NP testing to detect NCI and correlations with functional impairment and the presence of specific viral signatures among infected subjects. 60 HIV-1 seropositive antiretroviral-naive individuals and 56 seronegative control subjects were administered the International HIV Dementia Scale (IHDS) and assessed for functional impairment using the Karnofsky Performance Status Scale. 15 HIV infected patients and 11 controls were also administered a detailed NP battery. Blood samples from 8 infected subjects, 3 with evidence of NCI, were obtained for molecular analysis of HIV-1 strain. Unadjusted scores on the IHDS showed that, using a recommended total score cutoff of 10, 28.8% of the HIV-1 seropositive and 16.0% of seropositive individuals scored abnormally. The mean Karnofsky score for the HIV seropositive and seronegative groups were, respectively, 90.7 +12.2 and 98.8 +3.8 (p<0.0001). Results from testing using the full NP battery showed that overall the HIV seropositive group performed worse than the seronegative group, with effect sizes spanning from small (0.25 on the Trail Making Test A) to large (0.82 on Action Fluency), with an average effect size across the battery of 0.45, which approaches that which has been recorded in other international settings. Finally, sequencing of partial pol amplicons from viral isolates revealed that 2 of 3 patients with NCI were infected with subtype G virus and 1 with the circulating recombinant form (CRF) 02_AG; all 4 individuals without NCI were infected with CRF_02AG. These studies demonstrate the utility of conducting these studies for establishing the burden of NCI in the population of individuals with HIV-1 infection in Nigeria and for assessing the functional consequences and the virologic correlates of NCI.
doi:10.1007/s13365-012-0097-y
PMCID: PMC3717366  PMID: 22528480
10.  Intracranial Pressure Monitoring in Severe Traumatic Brain Injury in Latin America: Process and Methods for a Multi-Center Randomized Controlled Trial 
Journal of Neurotrauma  2012;29(11):2022-2029.
Abstract
In patients with severe traumatic brain injury (TBI), the influence on important outcomes of the use of information from intracranial pressure (ICP) monitoring to direct treatment has never been tested in a randomized controlled trial (RCT). We are conducting an RCT in six trauma centers in Latin America to test this question. We hypothesize that patients randomized to ICP monitoring will have lower mortality and better outcomes at 6-months post-trauma than patients treated without ICP monitoring. We selected three centers in Bolivia to participate in the trial, based on (1) the absence of ICP monitoring, (2) adequate patient accession and data collection during the pilot phase, (3) preliminary institutional review board approval, and (4) the presence of equipoise about the value of ICP monitoring. We conducted extensive training of site personnel, and initiated the trial on September 1, 2008. Subsequently, we included three additional centers. A total of 176 patients were entered into the trial as of August 31, 2010. Current enrollment is 81% of that expected. The trial is expected to reach its enrollment goal of 324 patients by September of 2011. We are conducting a high-quality RCT to answer a question that is important globally. In addition, we are establishing the capacity to conduct strong research in Latin America, where TBI is a serious epidemic. Finally, we are demonstrating the feasibility and utility of international collaborations that share resources and unique patient populations to conduct strong research about global public health concerns.
doi:10.1089/neu.2011.2019
PMCID: PMC3462405  PMID: 22435793
international; intracranial pressure monitoring; randomized controlled trial; traumatic brain injury
11.  Cytochrome P450-2D6 extensive metabolizers are more vulnerable to methamphetamine-associated neurocognitive impairment: Preliminary findings 
While neuropsychological deficits are evident among methamphetamine (meth) addicts, they are often unrelated to meth exposure parameters such as lifetime consumption and length of abstinence. The notion that some meth users develop neuropsychological impairments while others with similar drug exposure do not, suggests that there may be individual differences in vulnerability to the neurotoxic effects of meth. One source of differential vulnerability could come from genotypic variability in metabolic clearance of meth, dependent on the activity of cytochrome P450-2D6 (CYP2D6). We compared neuropsychological performance in 52 individuals with a history of meth dependence according with their CYP2D6 phenotype. All were free of HIV or hepatitis C infection and did not meet dependence criteria for other substances. Extensive metabolizers showed worse overall neuropsychological performance and were three times as likely to be cognitively impaired as intermediate/poor metabolizers. Groups did not differ in their demographic or meth use characteristics, nor did they evidence differences in mood disorder or other substance use. This preliminary study is the first to suggest that efficient meth metabolism is associated with worse neurocognitive outcomes in humans, and implicates the products of oxidative metabolism of meth as a possible source of brain injury.
doi:10.1017/S1355617710000779
PMCID: PMC3543816  PMID: 20727252
Substance abuse; CYP2D6; Polymorphisms; Neurotoxicity; Metabolism; Cognition
12.  HIV and Chronic Methamphetamine Dependence Affect Cerebral Blood Flow 
Human immunodeficiency virus (HIV) and methamphetamine (METH) dependence are independently associated with neuronal dysfunction. The coupling between cerebral blood flow (CBF) and neuronal activity is the basis of many task-based functional neuroimaging techniques. We examined the interaction between HIV infection and a previous history of METH dependence on CBF within the lenticular nuclei (LN). Twenty-four HIV−/METH−, eight HIV−/METH+, 24 HIV+/METH−, and 15 HIV+/METH+ participants performed a finger tapping paradigm. A multiple regression analysis of covariance assessed associations and two-way interactions between CBF and HIV serostatus and/or previous history of METH dependence. HIV+ individuals had a trend towards a lower baseline CBF (−10%, p=0.07) and greater CBF changes for the functional task (+32%, p=0.01) than HIV− subjects. Individuals with a previous history of METH dependence had a lower baseline CBF (–16%, p= 0.007) and greater CBF changes for a functional task (+33%, p=0.02). However, no interaction existed between HIV serostatus and previous history of METH dependence for either baseline CBF (p=0.53) or CBF changes for a functional task (p=0.10). In addition, CBF and volume in the LN were not correlated. A possible additive relationship could exist between HIV infection and a history of METH dependence on CBF with a previous history of METH dependence having a larger contribution. Abnormalities in CBF could serve as a surrogate measure for assessing the chronic effects of HIV and previous METH dependence on brain function.
doi:10.1007/s11481-011-9270-y
PMCID: PMC3251315  PMID: 21431471
Human immunodeficiency virus; Methamphetamine; Cerebral blood flow; Lenticular nuclei; Highly active antiretroviral therapy
13.  Dopamine receptor D3 genetic polymorphism (rs6280TC) is associated with rates of cognitive impairment in methamphetamine-dependent men with HIV: preliminary findings 
Journal of neurovirology  2011;17(3):239-247.
Macrophages are one of HIV-1’s principal targets and chiefly responsible for translocating HIV into the central nervous system (CNS). Previous research suggested an increase in macrophages being infected by HIV in the presence of methamphetamine (METH) or increased extracellular dopamine (DA). Experimental studies indicate that this is mediated by DA receptors, including DA receptor D3 (DRD3), which is expressed in macrophages. A single nucleotide polymorphism (SNP) of the DRD3 gene (rs6280TC) modulates its dopamine binding affinity, resulting in the possibility that inheriting a variant of this SNP increases macrophage susceptibility to HIV infection in the presence of METH and DA, particularly in the CNS where METH is sequestered, leading to cognitive impairment (CI). Thus, we conducted a retrospective clinical investigation to evaluate whether rs6280TC is associated with CI among HIV-positive METH users. We stratified 310 males by HIV serostatus (HIV-positive, -negative) and METH dependence (METH-positive, -negative) and then by rs6280TC genotype (CC, CT, and TT). Genotypic groups within each of four HIV/METH groups were compared for rates of CI. We hypothesized that only HIV-positive/METH-positive carriers of the C allele, which increases the DRD3’s binding to DA, would be more likely to develop CI. Cochran–Armitage test for trends in proportions yielded significant (p<0.05) association between three genotypes and impairment rates in the hypothesized order, but only among HIV-positive/METH-positive subjects. The results also confirmed that C allele carriers (CC and CT, 53.3%) in this group had higher impairment rates (p=0.05) than TT carriers (33.3%). These findings support the theory that rs6280TC influences the frequency of CI in HIV-positive/METH-positive males.
doi:10.1007/s13365-011-0028-3
PMCID: PMC3151555  PMID: 21491142
HIV; Methamphetamine; Cognitive impairment; SNP; Dopamine D3 receptor
14.  Are Time- and Event-based Prospective Memory Comparably Affected in HIV Infection?† 
According to the multi-process theory of prospective memory (ProM), time-based tasks rely more heavily on strategic processes dependent on prefrontal systems than do event-based tasks. Given the prominent frontostriatal pathophysiology of HIV infection, one would expect HIV-infected individuals to demonstrate greater deficits in time-based versus event-based ProM. However, the two prior studies examining this question have produced variable results. We evaluated this hypothesis in 143 individuals with HIV infection and 43 demographically similar seronegative adults (HIV−) who completed the research version of the Memory for Intentions Screening Test, which yields parallel subscales of time- and event-based ProM. Results showed main effects of HIV serostatus and cue type, but no interaction between serostatus and cue. Planned pair-wise comparisons showed a significant effect of HIV on time-based ProM and a trend-level effect on event-based ProM that was driven primarily by the subset of participants with HIV-associated neurocognitive disorders. Nevertheless, time-based ProM was more strongly correlated with measures of executive functions, attention/working memory, and verbal fluency in HIV-infected persons. Although HIV-associated deficits in time- and event-based ProM appear to be of comparable severity, the cognitive architecture of time-based ProM may be more strongly influenced by strategic monitoring and retrieval processes.
doi:10.1093/arclin/acr020
PMCID: PMC3081684  PMID: 21459901
AIDS dementia complex; Episodic memory; Executive functions; Neuropsychological assessment
15.  Impact of childhood trauma on functionality and quality of life in HIV-infected women 
Background
While there are many published studies on HIV and functional limitations, there are few in the context of early abuse and its impact on functionality and Quality of Life (QoL) in HIV.
Methods
The present study focused on HIV in the context of childhood trauma and its impact on functionality and Quality of Life (QoL) by evaluating 85 HIV-positive (48 with childhood trauma and 37 without) and 52 HIV-negative (21 with childhood trauma and 31 without) South African women infected with Clade C HIV. QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Patient's Assessment of Own Functioning Inventory (PAOFI), the Activities of Daily Living (ADL) scale and the Sheehan Disability Scale (SDS). Furthermore, participants were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Childhood Trauma Questionnaire (CTQ).
Results
Subjects had a mean age of 30.1 years. After controlling for age, level of education and CES-D scores, analysis of covariance (ANCOVA) demonstrated significant individual effects of HIV status and childhood trauma on self-reported QoL. No significant interactional effects were evident. Functional limitation was, however, negatively correlated with CD4 lymphocyte count.
Conclusions
In assessing QoL in HIV-infected women, we were able to demonstrate the impact of childhood trauma on functional limitations in HIV.
doi:10.1186/1477-7525-9-84
PMCID: PMC3198878  PMID: 21958030
HIV; Quality of Life; Childhood trauma; Functionality
16.  Longer Term Improvement in Neurocognitive Functioning and Affective Distress Among Methamphetamine Users Who Achieve Stable Abstinence 
Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little data is available on the possible added benefits of long-term sobriety. To address this, we performed detailed neuropsychological and affective evaluations in 83 MA-dependent individuals at a baseline visit and following an average one-year interval period. Among the 83 MA-dependent participants, 25 remained abstinent and 58 used MA at least once during the interval period. Thirty-eight non-MA-addicted, demographically matched healthy comparison (i.e., HC) participants were also examined. At baseline, both MA-dependent participants who were able to maintain abstinence and those who were not performed significantly worse than the healthy comparison subjects on global neuropsychological functioning and were significantly more distressed. At the one-year follow-up, both the long term abstainers and healthy comparison groups showed comparable global neuropsychological performance and affective distress levels, whereas the MA-dependent group who continued to use were worse than the comparison participants in terms of global neuropsychological functioning and affective distress. An interaction was observed between neuropsychological impairment at baseline, MA abstinence, and cognitive improvement, with abstinent MA-dependent participants who were neuropsychologically impaired at baseline demonstrating significantly and disproportionately greater improvement in processing speed and slightly greater improvement in motor abilities relative to the other participants. These results suggest partial recovery of neuropsychological functioning and improvement in affective distress upon sustained abstinence from MA that may extend beyond a year or more.
doi:10.1080/13803390903512637
PMCID: PMC2911490  PMID: 20198527
Methamphetamine; dependence; drug abstinence; cognition; central nervous system; affective disorders
17.  Preliminary evidence of ethnic divergence in associations of putative genetic variants for methamphetamine dependence 
Psychiatry research  2010;178(2):295-298.
Research into the biological processes that increase susceptibility to methamphetamine dependence has been conducted primarily in Asian populations. Using a case-control design this study’s purpose was to explore, among a population of methamphetamine-dependent Caucasians, six putative single nucleotide polymorphisms previously found to be associated with methamphetamine dependence in Asian populations. 193 non-psychotic males (117 methamphetamine-dependent and 76 controls) were genotyped for variants located in six genes (AKT1, ARRB2, BDNF, COMT, GSTP1, OPRM1). Genotypic and allelic frequencies, odds ratios, and 95% confidence intervals were calculated. None of the putative gene associations were significantly replicated in our sample of Caucasian men. Effect size comparisons suggest a trend toward allelic divergence for arrestin beta 2 (ARRB2) and glutathione S-transferase P1 (GSTP1) and allelic convergence for brain-derived neurotrophic factor (BDNF). Results provide preliminary support for further exploration and validation of candidate SNPs for METH dependence reported among Asian populations across other ethnic/ancestral groups.
doi:10.1016/j.psychres.2009.07.019
PMCID: PMC2902702  PMID: 20478633
AKT1; COMT; OPRM1; ARRB2; BDNF; GSTP1
18.  EQUIVALENCY OF SPANISH LANGUAGE VERSIONS OF THE TRAIL MAKING TEST PART B INCLUDING OR EXCLUDING “CH” 
The Clinical neuropsychologist  2008;22(4):662-665.
Spanish speakers commonly use two versions of the alphabet, one that includes the sound “Ch” between C and D and another that goes directly to D, as in English. Versions of the Trail Making Test Part B (TMT-B) have been created accordingly to accommodate this preference. The pattern and total number of circles to be connected are identical between versions. However, the equivalency of these alternate forms has not been reported. We compared the performance of 35 healthy Spanish speakers who completed the “Ch” form (CH group) to that of 96 individuals who received the standard form (D group), based on whether they mentioned “Ch” in their oral recitation of the alphabet. The groups had comparable demographic characteristics and overall neuropsychological performance. There were no significant differences in TMT-B scores between the CH and D groups, and relationships with demographic variables were comparable. The findings suggest that both versions are equivalent and can be administered to Spanish speakers based on their preference without sacrificing comparability.
doi:10.1080/13854040701476976
PMCID: PMC3059802  PMID: 17853122
Alphabet; CH; Equivalent forms; Spanish; Trails B
19.  Select Resistance-associated Mutations in Blood are Associated with Lower CSF Viral Loads and Better Neuropsychological Performance 
Virology  2009;394(2):243-248.
Background
When antiretroviral therapy does not fully suppress HIV replication, suboptimal levels of antiretrovirals can select for antiretroviral resistant variants of HIV. These variants may exhibit reduced replication capacity and result in lower viral loads in blood. Our study evaluated whether antiretroviral resistance was associated with viral loads in the cerebrospinal fluid (CSF) and better neuropsychological (NP) performance.
Methods
We enrolled ninety-four participants and each participant underwent a comprehensive neuromedical evaluation that used structured clinical assessments of medical history, ART and other medication use, comprehensive NP testing and neurological and general physical signs of disease. Blood was collected by venipuncture and all participants were offered lumbar puncture. Univariate and multivariate statistical methods were used to analyze the relationship between antiretroviral resistance, blood and CSF HIV RNA levels, substance use, and NP performance.
Results
Antiretroviral resistance, detected in blood, was associated with lower CSF viral loads (p<0.01) and better NP performance (p=0.04) in multivariate analyses, independent of past and current ARV use and blood viral loads (Model: p< 0.01). However, HIV RNA levels in CSF did not independently correlate with NP performance. Low viral loads in the CSF limited our ability to investigate the relationship between antiretroviral resistance detected in CSF and NP performance.
Conclusions
Even in the absence of ART, antiretroviral resistance-associated mutations correlate with better NP performance possibly because these mutations reflect reduced neurovirulence compared with wild-type HIV.
doi:10.1016/j.virol.2009.08.007
PMCID: PMC3046809  PMID: 19762060
20.  Assessing Neuropsychological Performance in a Migrant Farm Working Colonia in Baja California, Mexico: A Feasibility Study 
Neuropsychological impairments (NPI) can lead to difficulties in daily functioning and ultimately contribute to poor health outcomes. However, evidence for the feasibility of NPI assessment in resource-limited settings using tests developed in high literacy/high education cultures is sparse. The main objectives were to: (1) determine the feasibility and appropriateness of conducting neuropsychological assessments among a migrant farm worker population in Baja California, Mexico and (2) preliminary describe neuropsychological test performance in this unique population. A neuropsychological test battery was administered to 21 presumably healthy adults (8 men, 13 women) during a two-day international health services and research collaboration. All but one neuropsychological test (i.e. figure learning) was feasible and appropriate to administer to the study population. Contrary to expectations, participants performed better on verbal rather than nonverbal neuropsychological tests. Results support inclusion of neuropsychological tests into future studies among migrant farm worker populations in Baja California, Mexico.
doi:10.1007/s10903-011-9443-z
PMCID: PMC3132389  PMID: 21264515
Feasibility; Neuropsychological; Assessment; Mexico

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